Is F8 p.Val502Phe (c.1504G>T) pathogenic?

F8 p.Val502Phe (c.1504G>T) is classified Likely pathogenic in F8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-15). AlphaMissense: ambiguous (0.4461); Absent from gnomAD v4.1; Associated with hemophilia A.

What condition is associated with F8 p.Val502Phe (c.1504G>T)?

F8 p.Val502Phe (c.1504G>T) is associated with hemophilia A (ClinVar).

How common is F8 p.Val502Phe (c.1504G>T) in the general population?

F8 p.Val502Phe (c.1504G>T) is absent from gnomAD v4.1 (gnomAD).

How is Hemophilia A inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F8 p.Val502Phe (c.1504G>T)?

AlphaMissense predicts ambiguous (score 0.4461) — an in-silico prediction, not a clinical call.

F8 p.Val502Phe

c.1504G>T · rs2073393106 · VCV994422

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4461 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hemophilia A

Computational evidence

Protein change
AlphaMissense	0.4461	ambiguous
REVEL	0.632	indeterminate
SaProt	LLR -5.97	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 38 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F8
Protein: p.Val502Phe
Coding: c.1504G>T
MANE Select: NM_000132
dbSNP: rs2073393106
Type: single nucleotide variant
Location: chrX:154961108 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 502: the plastocyanin-like 3 domain; a β-strand; the f5/8 type a 2 domain

Full F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hemophilia A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hemophilia A (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

F8 c.6429+2T>A Pathogenic ★★★ same condition
F8 p.Ala111Thr Likely pathogenic ★★★ same condition
F8 p.Ala2220Pro Pathogenic ★★★ same condition
F8 p.Ala415Asp Likely pathogenic ★★★ same condition
F8 p.Ala415Val Pathogenic ★★★ ⚠ same condition
F8 p.Arg1768His Pathogenic ★★★ ⚠ same condition
F8 p.Arg1800His Pathogenic ★★★ same condition
F8 p.Arg2016Trp Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/f8-p-val502phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown